Disc-related back pain might have a new foe: gene therapy delivered by naturally derived nanocarriers. A recent study shows these can repair damaged discs in the spine and lower pain symptoms in mice. 

Researchers used mouse fibroblasts, a type of connective tissue cell, to create nanocarriers loaded with genetic material for a protein crucial to tissue development. This solution was injected into damaged discs in mice at the time of back injury. Over 12 weeks, imaging, tissue analysis, and tests revealed that the gene therapy restored structural integrity and function to degenerated discs and reduced signs of back pain.

“We have this unique strategy that’s able to both regenerate tissue and inhibit some symptoms of pain,” said co-senior author Devina Purmessur Walter, associate professor of biomedical engineering at The Ohio State University.

The findings suggest gene therapy could be a long-lasting alternative to opioids for managing debilitating back pain. “This can be used at the same time as surgery to actually boost healing of the disc itself,” said co-senior author Natalia Higuita-Castro, associate professor of biomedical engineering and neurological surgery at Ohio State. “Your own cells are actually doing the work and going back to a healthy state.”

Published recently in Biomaterials, the study builds on previous work in Higuita-Castro’s lab. Last year, they reported that nanocarriers called extracellular vesicles, loaded with anti-inflammatory cargo, curbed tissue injury in damaged mouse lungs. These carriers mimic the natural extracellular vesicles in humans, which carry messages between cells.

To create these vesicles, scientists applied an electrical charge to donor cells, opening holes in their membrane to deliver externally obtained DNA. This DNA converts to a specific protein and prompts the manufacture of more functional proteins. In this study, the cargo was a “pioneer” transcription factor protein called FOXF1, essential for tissue development and growth.

“Our concept is recapitulating development: FOXF1 is expressed during development and in healthy tissue, but it decreases with age,” Purmessur Walter explained. “We’re basically trying to trick the cells and give them a boost back to their developmental state when they’re growing and at their healthiest.”

In experiments, mice with injured discs treated with FOXF1 nanocarriers showed significant improvements compared to controls. The tissue plumped back up and became more stable, promoting range of motion, load-bearing, and flexibility in the spine. Behavioral tests showed the therapy decreased pain symptoms, though responses differed by sex – males and females had varying susceptibility to pain based on movement types.

The researchers highlighted the value of using universal adult donor cells to create these extracellular vesicle therapies, which don’t carry the risk of generating an immune response. Ideally, the gene therapy would function as a one-time treatment. “The idea of cell reprogramming is that you express this transcription factor, and the cell is then going to convert to this healthier state and stays committed to that healthier phenotype – and that conversion is not normally transient,” Higuita-Castro said. “So, in theory, you would not expect to have to re-dose significantly.”

Future experiments will test other transcription factors contributing to intervertebral disc development. The team also plans to test the therapy’s effects in older animals that model age-related degeneration and eventually in clinical trials for larger animals known to develop back problems.